Matrix metalloproteinase inhibitor regulates inflammatory cell migration by reducing ICAM-1 and VCAM-1 expression in a murine model of toluene diisocyanate-induced asthma

Abstract

Background: Matrix metalloproteinase-9 (MMP-9) has been reported to play a crucial role in the transmigration of neutrophils, lymphocytes, and eosinophils. Neutrophils, eosinophils, and lymphocytes migrate from the blood to the lungs in response to inflammatory mediators produced in the airways and are subsequently released into the circulation. This traffic is mediated by adhesion molecules. However, little is known about the migration of inflammatory cells through the endothelial and epithelial basement membranes in toluene diisocyanate (TDI)-induced asthma. Objectives: An aim of this study was to evaluate the effect of MMP inhibitors on the expression of ICAM-1 and VCAM-1 in the migration of inflammatory cells in a murine model of TDI-induced asthma. Methods: We used a murine model to investigate TDI-induced asthma to examine the possible involvement of ICAM-1 and VCAM-1 in the pathogenesis of that disease and the effect of MMP inhibitors on the expression of ICAM-1 and VCAM-1. Results: In mice, the following typical pathophysiologic features develop in the lungs: increased numbers of inflammatory cells and increased expression of MMP-9, ICAM-1, and VCAM-1 mRNA and protein. Administration of MMP inhibitors reduced the increased numbers of inflammatory cells and the increased expression of ICAM-1 and VCAM-1 mRNA expression and protein. In addition, MMP inhibitors significantly abrogated the increased expression of IL-1β, IL-4, and TNF-α mRNA in lung tissues and levels of IL-1β, IL-4, and TNF-α in bronchoalveolar lavage fluids after TDI inhalation. Conclusions: These results suggest that MMP inhibitors regulate inflammatory cell migration by reducing ICAM-1 and VCAM-1 expression and possibly also by suppressing IL-1β, IL-4, and TNF-α expression. (J Allergy Clin Immunol 2003;111:1278-84.)